Research Article Assessment of Hupu Gum for its ... · Assessment of Hupu Gum for its Mucoadhesive...

International Journal of Pharma Research & Review, Sept 2015; 4(9):9-20 ISSN: 2278-6074

Anu Pravallika Janipalli et.al, IJPRR 2015; 4(9) 9

Research Article

Assessment of Hupu Gum for its Mucoadhesive Property in the Design and Evaluation of Mucoadhesive Buccal Patches of Propranolol HCl *Anu Pravallika Janipalli, Lohithasu Duppala, Chaitanya Krishna Mylangam, Janaki Devi Sirisolla, Venkata Ramana Murthy Kolapalli Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, Andhra University College of Pharmaceutical Sciences, Andhra Pradesh- 530003, India.

ABSTRACT Objectives: There are no reports about assessment of the mucoadhesive property of formaldehyde treated hupu gum (HG). Hence the present study was undertaken to assessment of its mucoadhesive property of hupu gum in design of mucoadhesive buccal patches of Propanolol Hcl as a model drug. Methods: The prepared mucoadhesive buccal patches were compared with known muccoadhesive polymer, such as polyethylene oxide N 750. Poloxamer 407 is used as a penetration enhancer. The various physicomechanical parameters such as weight variation, folding endurance, thickness, surface pH, drug content, swelling studies and various ex vivo mucoadhesion parameters like mucoadhesive strength and force of adhesion were evaluated. In vitro diffusion studies as well as ex vivo drug release studies were performed. Results and conclusion: The results of the present investigation concluded that the formaldehyde treated hupu gum used as mucoadhesive polymer in development of buccal patches of propranolol Hcl were prepared by solvent casting method. Hupu gum is highly viscous, difficult to form buccal patches, due to this reason it is exposed to formaldehyde for 1hr to reduce its swelling nature. However, the variation in the release profile of propranolol Hcl due to different in the drug to polymer ratio. Finally, concluded that the formaldehyde treated hupu gum used as a mucoadhesive polymer. Keywords: Formaldehyde treated hupu gum, in vitro diffusion studies, poloxamer 407, polyethylene

oxide N 750 and propranolol Hcl

Received 12 August 2015 Received in revised form 24 August 2015 Accepted 27 August 2015 *Address for correspondence: Anu Pravallika Janipalli, Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, Andhra University College of Pharmaceutical Sciences, Andhra Pradesh- 530003, India. E-mail: [email protected] _________________________________________________________________________________________________________________________ INTRODUCTION In present days, researchers were focused on drug delivery system in a specific region of the body for enhancing bioavailability and to minimize the dose dependent side effects. Buccal drug delivery system provides a promising alternate to other conventional systemic drug administrative methods as well as buccal mucosa acts as an excellent site for the absorption of drugs due to its relatively permeable with rich blood supply [1, 2]. The buccal route of administration of drugs which facilitates that drug molecules were directly enter into the systemic circulation, to avoid the first-pass metabolism as well as drug degradation in the harsh gastrointestinal(GI) environment, which are associated with oral route of administration. The buccal route is safe, easily accessible for self-medication and

easily accepted by patients. Buccal mucoadhesive patches can be easily administered and removed from site of application, also to stop the input of drug whenever desired. Buccal mucoadhesive patches provide flexibility than other drug delivery systems [3-6]. Hupu gum is having good swelling index and moderate viscosity with various applications such as additive in food industry, in the printing industry and adhesive in chemical industry. Hupugum, a natural polysaccharide was found to be safe and non toxic up to 5%. The earlier reports on hupu gum revealed that it is used as carrier in the design and evaluation of solid mixtures of rofecoxib for dissolution enhancement [7]. So, hupu gum was selected for its application in the design of mucoadhesive buccal patches of



propranolol HCl as model drug. Hupu gum (Kondagogu, Kolha or Silk-cotton) is the dried gummy exudate obtained from the deciduous tree of “Cochlospermum religiosum (L.) Alston” (synonym Cochlospermum gossypium (L) D.C.), belongs to family Cochlospermaceae (synonym Bixaceae). Hupu gum tree is abundantly found in hills and forests of Chittoor, East Godavari districts in Andhra Pradesh, Mayurbhanj district in Odisha, India [8]. Its applicability is reported for industries like paper, printing gum, nicotine sprays and in the preparations of lotions and pastes, it was not investigated for its applicability in the pharmaceutical field [9]. Propranolol HCl was taken as model drug. It is chemically 1-naphthalen-1-yloxy-3-(propan-2-ylamino) propan-2-ol and it is a synthetic, sympatholytic, non-selective beta-adrenergic receptor blocker with antianginal, antiarrhythmic (class II) and antihypertensive properties. It is competitively antagonizes beta-adrenergic receptors, thereby inhibiting beta-adrenergic reactions, such as vasodilation, and negative chronotropic and inotropic effects. It is soluble in alcohol, slightly soluble in chloroform, practically insoluble in ether. Propranolol HCl undergoes extensive and highly variable hepatic first-pass metabolism following oral route of administration [10-12]. In this present work an attempt to study the mucoadhesive property of formaldehyde exposed hupu gum on propranolol HCl taken as a model drug, finally compared with the known mucoadhesive polymers such as polyethylene oxide (PEO) N 750 and the prepared mucoadhesive buccal patches were evaluated. The buccal mucoadhesive patches were prepared by solvent casting method. MATERIALS AND METHODS Propranolol hydrochloride was obtained as gift sample from Dr. Reddy’s Laboratories Ltd, Hyderabad, India. Hupu gum of Grade-I quality was purchased from M/s. Girijan Co-op Corporation Ltd., Visakhapatnam, India. Polyethylene oxide(PEO N 750) and poloxamer 407 were purchased from Sigma Aldrich, Steinheim, Germany. All the other chemicals were used of A.R grade, satisfying pharmacopoeial specifications.

Preparation of mucoadhesive buccal patches Hupu gum is highly viscous and difficult to form patches. Hence it is exposed to formaldehyde for 1hr to reduce its swelling nature. To produce a unidirectional release, one side of the drug layer is coated with impermeable backing layer (cellulose acetate).600 mg of cellulose acetate was weighed and dissolved in 20 ml of acetone, to this 0.5 ml of glycerine was added as per the formula shown in (Table 1). The prepared solution was poured into a petriplate, kept at room temperature and allowed to dry. Thus, the backing layer was prepared. Required amounts of polymer, drug and penetration enhancer as per the formula shown in (Table 1) (priorly exposed hupu gum to formaldehyde and PEO) were dissolved in water separately. The solution containing drug and penetration enhancer (poloxamer 407) was added to the prepared polymer solution and stirred continuously using magnetic stirrer. The prepared solution was poured uniformly into a petriplate containing backing layer by solvent casting technique, and allowed to dry in oven at 40 0C. Fourier transform infrared spectroscopy (FTIR) FTIR spectra of hupu gum, pure propranolol Hcl, optimized hupu gum formulation (PHG10) and PEO N 750 formulations (PPEO7) compatibility were studied by KBr pellet method using FTIR spectrophotometer (M/s. Perkin–Elmer, 841, Spectrum one).The scanning range was 400-4000 cm-1 and resolution was 1 cm-1. To study any possible interaction between drug and the plant gum FTIR spectroscopic analysis were carried out. Infrared absorbance data was collected over the wave number ranged from 4000 cm-1 to 400 cm-1 and was expressed in cm-1 Mucoadhesive strength measurement Detachment force was measured on a modified balance in which the right pan was removed. A plastic beaker was kept in left pan and both the sides were balanced by weights. The buccal mucosal tissue of porcine was collected from the local slaughter house and stored in normal saline solution.



Table 1: Formualtion chart of Propranolon Muccoahesive Buccal Patches

Formulation code*

Propranolol HCl (mg) PEO N 750 (mg) FE-HG (mg)

Poloxamer 407(mg)

PHG 1 283.5 - 999.3 - PHG 2 283.5 - 1134 - PHG 3 283.5 - 1417 - PHG 4 283.5 - 999.3 40 PHG 5 283.5 - 1134 40 PHG 6 283.5 - 1134 80 PHG 7 283.5 - 1417 40 PHG 8 283.5 - 1417 80 PHG 9 283.5 - 1417 120

PHG 10 283.5 - 1417 160 PPEO 1 567 567 - - PPEO 2 567 1134 - - PPEO 3 567 1417.5 - - PPEO 4 567 1701 - - PPEO 5 567 1417.5 - 40 PPEO 6 567 1417.5 - 80 PPEO 7 567 1417.5 - 120 PPEO 8 567 1701 - 40 PPEO 9 567 1701 - 80

PPEO 10 567 1701 - 120 PPEO 11 567 1984.5 - 160 PPEO 12 567 2268 - 160

*All formulations contains Cellulose acetate-600 mg, Glycerine- 0.5 ml, Acetone- 20 ml. FE-HG -Formaldehyde exposed Hupu gum, PEO N 750 -Polyethylene oxide N 750

The underlying connective tissue was separated and washed with pH 6.6 phosphate buffer. The mucosal membrane was carefully cut and attached to the glass slide with the mucosal side facing outwards using cyanoacrylate glue and this slide was attached to the petri plate and it was placed on the right side of the balance. The patch was attached to the glass slide facing the drug polymer layer outwards using cyanoacrylate glue. The glass slide was suspended on the right hand side using a non elastic thread and the height of thread was adjusted. The mucous layer and the patch were wetted with pH 6.6 phosphate buffer and the patch was fixed to the mucus layer by applying a little pressure with the thumb and kept undisturbed for 5 min. On left hand side, water was added slowly in to a plastic beaker with the help of a burette till the patch just separated from the membrane surface. The weight of water in grams required to detach the patch was noted. The results were shown in (Table 2). Mucoadhesion strength was calculated in Newtons by using the formula:

Force of adhesion (N) = Mucoadhesive strength X 9.81 / 1000. Determination of ex vivo residence time The ex vivo residence time was determined using USP dissolution apparatus II. The buccal mucosa of porcine which was previously washed was attached to the glass slide with the mucosal side facing outwards using cyanoacrylate glue. This was horizantally fixed to paddle of the dissolution apparatus. Drug polymer layer of patch was wetted with 0.5 ml of pH 6.6 phosphate buffer and attached to the mucus tissue with a little pressure to develop initial contact. 900 ml of pH 6.6 phosphate buffer was used as medium maintained at 37°C at 20 rpm. The time necessary for complete erosion or detachment of the patch from the mucosal surface was recorded. The results were shown in (Table 2). Weight variation and thickness For evaluation of weight variation three patches (each of 1sqcm) of every formulation were taken and weighed individually on a digital balance. The average weights were calculated. Similarly, three patches (each of 1sqcm) of each formulation



were taken and the film thickness was measured using micrometer screw gauge at three different places and the mean value was calculated and shown in the (Table 3). Surface pH study To evaluate the surface pH, buccal patches were left to swell for 2hrs in the 6.6 phosphate buffer. The surface pH was measured by means of a pH paper (range of 2-14) placed on the surface of the swollen patch and pH was measured and values are shown in (Table 3). Folding endurance The folding endurance of patches was determined by folding a patch repeatedly at the same place till it broke or was folded up to 300 times without breaking. The number of times, the film could be folded at the same place without breaking was noted as folding endurance in the (Table 3). Drug content To estimate the drug content for hupu gum(5mg/sqcm) and PEO N 750 (10mg/sqcm), three patch units (each of 1sqcm) from each formulation were taken and dissolved in 20 ml of 6.6 phosphate buffer by continues stirring using magnetic stirrer. The solution was diluted suitably with the pH 6.6 phosphate buffer and analysed at 289 nm using UV spectrophotometer and results are shown in the (Table 3). Swelling studies 2.5% agar gel was prepared and poured in to a petri dish and allowed to solidify. Buccoadhesive patches were weighed individually (W1) and placed in petri dish with the drug polymer layer facing agar gel and allowed to swell. The patches were removed at time intervals of 1, 2, 3, 4, 5, 6, 7 and 8 hrs from the petri dish and excess surface water was removed carefully with the tissue paper. The swollen patches were then reweighed (W2). This experiment was performed in triplicate. The swelling index was calculated according to the following

equation and results are shown in the (Fig. 2). Swelling index = (W2-W1)/W1× 100 In-vitro diffusion studies The release studies were determined by Franz diffusion cell. The dialysis membrane pore size of 50mm acts as a permeability barrier and pH 6.6 phosphate buffer acts as a

medium. The patch of desired size was placed on the dialysis membrane and kept between 2 compartments. The receptor compartment contains 30 ml of pH 6.6 phosphate buffer and hydrodynamics was maintained by stirring with a magnetic bead at 400-500 rpm. At regular intervals 2 ml of sample was withdrawn from the receptor compartment and replaced with 2 ml of fresh medium. The samples collected were diluted suitably and analysed at 289 nm using UV spectrophotometer and the results were shown in the (Fig. 3). Release kinetics The analysis of drug release mechanism from a pharmaceutical dosage form is an important but complicated process and is practically evident in the case of matrix systems. As a model dependent approach, the dissolution data was fitted to popular release models such as zero-order, first-order, Higuchi, erosion and peppas equations. The order of drug release from matrix systems was determined by using zero order kinetics or first order kinetics. The mechanism of drug release from matrix systems was studied by using Higuchi equation, erosion and peppas equation and the results were shown in the (Table 4). Ex-vivo release studies Ex vivo buccal permeation of propranolol HCl was studied with fresh porcine buccal mucosa as a barrier membrane. The buccal pouch of freshly sacrificed animal was procured from local slaughter house and was used within 2 hrs. The buccal mucosa was excised and trimmed evenly from the sides underlying connective tissue was removed. The membrane was washed with mammalian ringer solution and then with phosphate buffer (pH 6.6). The Ex vivo permeation studies were carried out using the modified Franz diffusion cell at 37ºC ± 0.2ºC. A patch of (1sqcm) of optimised formulation under study was placed in intimate contact with the excised porcine buccal mucosa magnetic bead was placed in the receptor compartment filled with 30 ml of pH 6.6 phosphate buffer. The cell contents were stirred with a magnetic stirrer and temperature of 37 ºC ± 0.2 ºC was maintained throughout the experiment. The samples were withdrawn at predetermined time intervals, filtered, diluted suitably, and



then analyzed using UV-spectrophotometer at 289 nm and the results were shown in (Fig. 4). RESULTS AND DISCUSSION Fourier transform infrared spectroscopy (ftir) The FTIR spectra of pure drug propranolol HCl, pure polymers hupu gum, PEO N 750 and penetration enhancer poloxamer 407 and their respective selected formulations PHG10 (1:5) and PPEO7 (1:2.5) are shown in

(Fig. 1). Presence of hupu gum and PEO N 750 and other excipients did not produce any major shift in principal peaks of propranolol HCl and also the presence of one ingredient did not produce shift in the peaks of other ingredients. This indicates that there is no interaction between drug and the excipients used in the study. Hence FTIR spectral analysis proved the compatibility of the drug and excipients used in the study.

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c)

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Figure 1: FTIR spectrum of a)Prapanolo Hcl; b) hupu gum; c)PEO N 750; d) Hupu gum formulation (PHG10); e) PEO N 750 formulations (PPEO7)

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Mucoadhesive strength measurement Mucoadhesive strength measurement was conducted for all formulations prepared with hupu gum and PEO N 750. Formulations containing hupu gum with different drug to polymer ratios are PHG1(1:3.5), PHG 4 (1:3.5), PHG 2(1:4), PHG 5(1:4), PHG 6 (1:4) and PHG 3(1:5), PHG7(1:5), PHG 8(1:5), PHG 9(1:5), PHG 10 (1:5) having 0.1%, 0.2%, 0.3%, 0.4% of penetration enhancer (poloxamer 407) respectively were shown in the (Table 2). While, those prepared with PEO N 750 are PPEO1 (1:1), PPEO2 (1:2), PPEO3(1:2.5), PPEO5(1:2.5), PPEO6(1:2.5), PPEO7 (1:2.5), PPEO4(1:3), PPEO8(1:3), PPEO9(1:3), PPEO10 (1:3), PPEO11 (1:3.5) and PPEO12 (1:4) with 0.1%, 0.2%, 0.3%, 0.4% of penetration enhancer respectively were shown in the (Table 2). The maximum mucoadhesion force (N) was observed for the formulations PHG10 (0.148) and PPEO12 (0.125) where as low mucoadhesion force (N) for the formulations PHG1 is 0.096 and PPEO1 is 0.067. Among the formulations prepared with hupu gum (PHG10) having mucoadhesive force (N) 0.148 and for PEO N750 (PPEO7) having mucoadhesive force (N) 0.096.

Ex vivo residence time Evaluation of ex vivo residence time was conducted for all formulations prepared with hupu gum and PEO N 750. Formulations containing hupu gum with different drug to polymer ratios are PHG1(1:3.5), PHG 4 (1:3.5), PHG 2(1:4), PHG 5(1:4), PHG 6 (1:4) and PHG3(1:5), PHG7 (1:5), PHG 8(1:5), PHG 9 (1:5), PHG10 (1:5) having 0.1%, 0.2%, 0.3%, 0.4% of penetration enhancer (poloxamer 407) respectively were shown in the (Table 2). While, those prepared with PEO N 750 are PPEO1 (1:1), PPEO2 (1:2), PPEO3 (1:2.5), PPEO5 (1:2.5), PPEO6 (1:2.5), PPEO7 (1:2.5), PPEO4(1:3), PPEO8(1:3), PPEO9(1:3), PPEO10 (1:3), PPEO11 (1:3.5) and PPEO12 (1:4) with 0.1%, 0.2%, 0.3%, 0.4% of penetration enhancer respectively were shown in the (Table 2). Ex vivo residence time varied from 6-8.5 hrs for the formulations prepared with hupu gum while those prepared with PEO N 750 varied from 1.5-4 hrs. It was found that as the concentration of polymer increased, the time of residence increased. Among the formulations prepared with hupu gum (PHG10) and PEO N 750 (PPEO7) showed 8.5 and 2.5 hrs respectively.

Table 2: Ex vivo residence time and mucoadhesive strength of propranolol HCl patches

Formulation Code Mucoadhesive residence time (Mean ± s.d)(n=3)

Mucoadhesion Force (N) (mean ± s.d)(n=3)

PHG1 6 ± 0.56 0.096 ± 0.097

PHG2 7 ± 0.86 0.111 ± 0.098 PHG3 8 ± 0.63 0.132 ± 0.135 PHG4 6 ± 0.32 0.100 ± 0.072 PHG5 7 ± 0.65 0.117 ± 0.031 PHG6 7 ± 0.19 0.123 ± 0.179 PHG7 8 ± 0.49 0.134 ± 0.044 PHG8 8 ± 0.82 0.137 ± 0.017 PHG9 8 ± 0.16 0.143 ± 0.208

PHG10 8.5 ± 0.56 0.148 ± 0.069 PPEO1 1.5 ± 0.47 0.067 ± 0.137 PPEO2 2 ±0.23 0.075 ± 0.241 PPEO3 3 ± 0.85 0.084 ± 0.256 PPEO4 3.5 ± 0.95 0.095 ± 0.251 PPEO5 2 ± 0.32 0.086 ± 0.103 PPEO6 2.5 ± 0.65 0.09 ± 0.321 PPEO7 2.5 ± 0.83 0.096 ± 0.305 PPEO8 3 ± 0.88 0.100 ± 0.319 PPEO9 3.5 ± 0.56 0.105 ± 0.271

PPEO10 3.5 ± 0.63 0.107 ± 0.071 PPEO11 4 ± 0.65 0.114 ± 0.233 PPEO12 4 ± 0.56 0.125 ± 0.653



Weight variation and thickness Weight of the patches was found to be in the range of 33.1 to 48 mg for hupu gum and PEO N750 in the range of 39.2 to 62.8 mg. As the proportion of the polymers is increasing, correspondingly the weight of the patches is increasing. The thickness of the buccal patch increases with increase in the amount of polymer. The maximum thickness was observed for the formulations PHG10 (0.586) and PPEO12 (0.556) where as minimum thickness was observed for the formulations PHG1 is and PPEO1 is 0.493 and 0.303.The average thickness of the cellulose acetate prepared backing layer was 0.3 mm. Among all the formulations

prepared with hupu gum (PHG 10) showed thickness 0.586 mm and for PEO N750 (PPEO7) showed thickness 0.466 mm. Surface pH study The surface pH of prepared patches was measured with pH paper, values were found to be in the range of 6-7. This shows that the formulations were suitable for buccal drug delivery as pH was within the range of buccal cavity. Folding endurance All the patches did not show any deformation of patch after 300 times folding, which results that the all are having satisfactory flexibility.

Table 3: Characteristics of propranolol HCl patches Formulation Code

Thickness (mean ± s.d) (n=3)

Weight variation (mean ± s.d) (n=3)

Surface pH

Folding endurance

Drug content (mean ± s.d) (n=3)

PHG1 0.493 ± 0.003 33.10 ± 0.31 6-7 > 300 96.23 ± 0.23 PHG2 0.523 ± 0.003 40.23 ± 0.11 6-7 > 300 97.56 ± 0.56 PHG3 0.563 ± 0.003 44.20 ± 0.25 6-7 > 300 98.16 ± 0.12 PHG4 0.500 ± 0.003 34.21 ± 0.14 6-7 > 300 98.22 ± 0.52 PHG5 0.523 ± 0.003 40.41 ± 0.45 6-7 > 300 95.26 ± 0.15 PHG6 0.526 ± 0.003 40.80 ± 0.23 6-7 > 300 97.13 ± 0.23 PHG7 0.570 ± 0.003 44.40 ± 0.08 6-7 > 300 98.66 ± 0.15 PHG8 0.573 ± 0.003 45.00 ± 0.33 6-7 > 300 98.11 ± 0.12 PHG9 0.576 ± 0.003 47.50 ± 0.32 6-7 > 300 95.13 ± 0.45 PHG10 0.586 ± 0.003 48.00 ± 0.26 6-7 > 300 99.16 ± 0.16 PPEO1 0.303 ± 0.003 39.20 ± 0.31 6-7 > 300 96.63 ± 0.27 PPEO2 0.416 ± 0.003 39.40 ± 0.23 6-7 > 300 97.81 ± 0.11 PPEO3 0.446 ± 0.003 45.40 ± 0.11 6-7 > 300 96.72 ± 0.26 PPEO4 0.523 ± 0.003 50.80 ± 0.21 6-7 > 300 98.52 ± 0.11 PPEO5 0.456 ± 0.003 45.80 ± 0.33 6-7 > 300 95.53 ± 0.41 PPEO6 0.456 ± 0.003 46.00± 0.51 6-7 > 300 97.62 ± 0.50 PPEO7 0.466 ± 0.003 47.4 ± 0.63 6-7 > 300 99.45 ± 0.13 PPEO8 0.526 ± 0.003 51.00 ± 0.23 6-7 > 300 96.85 ± 0.12 PPEO9 0.536 ± 0.003 51.2 ± 0.22 6-7 > 300 99.76 ± 0.15 PPEO10 0.54 ± 0.003 52.6 ± 0.55 6-7 > 300 98.56 ± 0.15 PPEO11 0.546 ± 0.003 56.7 ± 0.12 6-7 > 300 96.53 ± 0.61 PPEO12 0.556 ± 0.003 62.8 ± 0.23 6-7 > 300 97.71 ± 0.18

Swelling studies The patches prepared with hupu gum and PEO N750 has shown good swelling property and swelling index was increased with increase in the concentration for both the polymers. Formulations prepared with hupu gum has shown high swelling index than formulations prepared with PEO N750. Swelling index was measured for 8 hrs. The % swelling index is increased up to 5 hrs for PEO N750, but after that there was a

decrease in the swelling of PEO N750 formulations where as hupu gum gradual swelling was observed. In-vitro diffusion studies The in vitro diffusion studies of the formulated patches revealed that drug release from the patches depends on the concentration of polymer used in the formulation. In the present work, the formulations are designed to release the drug over a period of 6 hrs. Formulations



prepared with hupu gum were PHG 6 and PHG 10 released 94% and 99% of the drug in 6 hrs respectively are shown in the (Fig. 3). Formulations prepared with PEO N 750 were PPEO1 and PPEO7 released 100% and 99.5% of the drug in 3 hrs, and 6 hrs respectively are shown in the (Fig. 3). Based on the in vitro drug release studies and other the evaluated me formulations prepared with hupu gum and PEO N 750 PHG10 and PPEO7 were selected as the optimized formulations as these formulations showed 99% and 99.5% drug release for a desired period of 6 hrs which is suitable in the design of buccoadhesive patches of propranolol hydrochloride.

Figure 2: Swelling index studies of different formulations of propranolol HCl patches

0

10

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30

40

50

60

70

80

90

100

0 1 2 3 4 5 6

% D

rug r

elea

sed

Time(hr)

PHG2

PHG5

PHG6



Figure 3: Diffusion profile of various mucoadhesive buccal patches of propranolol HCl Release kinetics In order to establish the mechanism of drug release, the data was fitted into popular exponential equations namely zero order, first order, Higuchi, Peppas and erosion and release kinetics of all formulations are shown in the (Table 4). The drug release kinetics from the hupu gum based formulation followed first-order kinetics (0.921-0.996) except the formulations PHG1, PHG9 and PHG10 which followed zero-order kinetics(0.946-0.992).The drug release kinetics from the PEO N750 based formulations also followed first order kinetics (0.918-0.992) except the formulations PPEO1, PPEO7 and PPEO9 which followed zero order kinetics(0.951-0.992). The relative contributions of drug diffusion and matrix erosion to drug release were further confirmed by subjecting the diffusion data to Higuchi and erosion models. It was found that all the formulations made with hupu gum and PEO N 750 followed diffusion mechanism (0.975-0.999) except the formulations PHG1, PHG4, PPEO4, PPEO5, and PPEO6 followed erosion mechanism (0.965-0.983) as indicated by their ‘r’ values. Also, the type of diffusion was non-Fickian diffusion as observed from the ‘n’ values of Peppas equation which were ranging from (0.458-0.884). Ex-vivo release studies Ex vivo drug release studies were done for the optimized formulation of hupu gum (PHG10) and PEO N 750 (PPEO). PHG10 showed 90% drug release whereas PPEO7

0

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120

0 1 2 3 4 5 6

% D

rug

rel

ease

d

Time(hr)

PPEO1

PPEO2

PPEO3

PPEO4



showed 91.5% drug release. The release rate was decreased in ex-vivo studies when

compared to in vitro studies.

Table 4: Correlation coefficient (r) values and release kinetics of propranolol HCl muccoadhesive buccal patches Formulation code

Zero order First order Peppas Higuchi Erosion K0 r K1 r N r r R

PHG1 19.53 0.946 0.356 0.99 0.458 0.999 0.912 0.965 PHG2 15.21 0.966 0.264 0.98 0.548 0.981 0.991 0.981 PHG3 19.53 0.958 0.133 0.977 0.548 0.959 0.986 0.973 PHG4 20.03 0.991 0.377 0.996 0.808 0.996 0.931 0.976 PHG5 12.57 0.955 0.294 0.989 0.508 0.987 0.994 0.986 PHG6 13.9 0.958 0.435 0.969 0.514 0.993 0.991 0.983 PHG7 10.11 0.958 0.294 0.983 0.514 0.995 0.991 0.980 PHG8 13.34 0.991 0.435 0.995 0.764 0.988 0.983 0.973 PHG9 14.26 0.990 0.377 0.945 0.673 0.973 0.975 0.975 PHG10 15.28 0.992 0.488 0.921 0.693 0.984 0.979 0.971 PPEO1 22.01 0.951 0.985 0.918 0.521 0.995 0.995 0.941 PPEO2 12.2 0.817 0.287 0.929 0.499 0.985 0.985 0.898 PPEO3 10.48 0.967 0.188 0.992 0.525 0.997 0.997 0.987 PPEO4 12.21 0.971 0.188 0.986 0.870 0.957 0.957 0.983 PPEO5 13.75 0.973 0.237 0.991 0.866 0.962 0.962 0.988 PPEO6 12.48 0.975 0.732 0.976 0.508 0.970 0.970 0.979 PPEO7 14.49 0.983 0.534 0.866 0.581 0.986 0.986 0.943 PPEO8 15.16 0.975 0.294 0.987 0.852 0.986 0.986 0.984 PPEO9 15.88 0.992 0.336 0.965 0.884 0.986 0.986 0.981 PPEO10 12.13 0.880 0.384 0.979 0.775 0.991 0.991 0.966 PPEO11 11.78 0.926 0.303 0.974 0.528 0.999 0.999 0.973 PPEO12 11.49 0.925 0.276 0.982 0.662 0.992 0.992 0.974

Figure 4: Release profile of mucoadhesive buccal patches of propranolol Hcl CONCLUSION Thus, the results of the present investigation concluded that the formaldehyde treated hupu gum used as mucoadhesive polymer in development of buccal patches of propranolol Hcl were prepared by solvent casting method. Hupu gum is highly viscous,

difficult to form buccal patches, due to this reason it is exposed to formaldehyde for 1hr to reduce its swelling nature. However, the variation in the release profile of propranolol Hcl due to different in the drug to polymer ratio. Our results supported that formaldehyde exposed hupu gum is suitable



natural polysaccharide for development mucoadhesive buccal patches. CONFLICT OF INTEREST The authors confirm that this article content has no conflicts of interest. ACKNOWLEDGEMENTS Declared none. PATIENT CONSENT Declared none. REFERENCES 1. Hoogstrate AJ, Verhoef JC, Tuk B, Pijpers A,

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